Preparing process for Eptifibatide

A new process and resin technology, applied in the direction of blood diseases, extracellular fluid diseases, peptides, etc., can solve the problems affecting the purity of crude products, the reaction is not easy to complete, and the difficulty of purification is increased, so as to achieve easy tracking, production cost reduction, and synthesis process The effect of mild conditions

Inactive Publication Date: 2004-06-02
GL BIOCHEM SHANGHAI +1
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Problems solved by technology

The BOC strategy solid-phase method also has two disadvantages: 1. In the process of converting arginine into homoarginine, it is carried out under heterogeneous conditions, and the reaction is not easy to complete
And whether this degree of conversion is completely impossible to detect and track on the resin, thus af...

Method used

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  • Preparing process for Eptifibatide
  • Preparing process for Eptifibatide
  • Preparing process for Eptifibatide

Examples

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Embodiment Construction

[0026] With reference to accompanying drawing, a kind of new process of preparing Efibuta, its preparation process step is:

[0027] a. Fmoc-Rink Amide AM resin in 20% piperidine, DMF, room temperature for 20 minutes, after de-Fmoc-protection to get H 2 N-Rink Amide AM resin;

[0028] b. According to the method of solid phase synthesis in H 2 On the N-Rink Amide AM resin, the condensation reaction is carried out sequentially to connect the following protected amino acids: Fmoc-Cys(Trt)-OH; Fmoc-Pro-OH; Fmoc-Trp(Boc)-OH; Fmoc-Asp(tBu)-OH; Fmoc -Gly-OH; (not shown in the figure) to obtain Fmoc-Cys(Trt)-NH-Rink Amide AM resin and the resin connected to the subsequent protected amino acid, the selected condensing agent is HBTU, HOBt, DMF, and the reaction time is 2 hours at room temperature .

[0029] c. In the meantime, use piperidine to remove the Fmoc-protecting group to obtain NH 2 -Gly-Asp(OtBu)-Trp-Pro-Cys(Trt)-NH-Rink AM resin, using Kaiser test to detect the reaction p...

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Abstract

The present invention relates to the preparation of cyclic peptide, and is especially new Fmoc-solid phase process of preparing Eptifibatide. The new process is superior to liquid phase process, which has long synthesis period, and BOC solid phase process, which uses virulent and corrosive material. The technological scheme is that the Eptifibatide preparing process includes the following steps: eliminating Fmoc protection of Fmoc-Rink Amide AM resin to obtain H2N-Rink Amide AM resin; connecting various protective amino acids successively to obtain corresponding resin; eliminating Fmoc-protection radical and Kaiser test to detect reaction procedure; preparing S-triphenyl mercapto propionyl-N, N-ditert butyl oxycarbonyl-homoarginine with lysine; grafting S-triphenyl mercapto propionyl-N, N-ditert butyl oxycarbonyl-homoarginine; eliminating side chain protecting radical and resin to reduce into coarse product; and cyclization, oxidation, HPLC tracking purification to obtain pure product.

Description

1. Technical field [0001] The invention relates to a preparation process of cyclic peptides, in particular to a new process for preparing Efibuta by using the Fmoc-strategy solid-phase method. 2. Background technology [0002] Epifibatide is a cyclic peptide containing mercaptopropionyl and six amino acid residues, and it is the main active ingredient of the cardiovascular drug Intergrelin. Molecular formula: C 35 h 49 N 11 o 9 S 2 . At present, the manufacturer of this product in the world is Bachem Company in Switzerland. The two lines they use are: liquid phase method and Boc-strategy solid phase method. The preparation process of the liquid phase method includes: 1. The product Boc-Lys(Tfa)-Gly-OMe obtained by condensation of Gly-OMe and Boc-Lys(Tfa)-OH reacts with Mpa(Trt)-ONSu to obtain the product Mpa(Trt)- Lys(Tfa)-Gly-OMe, guanidinylation, saponification, to get Mpa(Trt)-Har-Gly-OH (fragment 1); 2, Z-Asp(OtBu)-OH and Trp-Pro-OMe condensation reaction, Obtain...

Claims

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Application Information

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IPC IPC(8): A61P7/02C07K7/64
Inventor 徐红岩
Owner GL BIOCHEM SHANGHAI
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